Rat Endogenous Intoxication Level under Experimental Nephropathy and Reduced Glutathione Application

2021 ◽  
Vol 6 (5) ◽  
pp. 63-68
Author(s):  
V. V. Bevzo ◽  

The purpose of the study, therefore, was to investigate the content of substances of low and medium molecular weight, total and tyrosine-containing peptides and to assess the level of endogenous intoxication of the rat organism under conditions of experimental nephropathy and the use of reduced glutathione. Materials and methods. The experiment was performed on nonlinear white rats weighing 160-180 g. The animals were in a vivarium with a constant temperature (18-22°C), relative humidity (50-55%) in individual exchange cells in the formed groups, on a constant balanced mode of a diet with free access to water and food. Nephropathy was modeled by a single intraperitoneal injection of folic acid at a dose of 250 mg/kg. Glutathione was administered intragastrically (100 mg/kg) for 7 days after folic acid intoxication. Results and discussion. Under conditions of nephropathy in the blood serum of rats, an increase in the level of molecules of average weight was observed by 2 times, as well as low-molecular substances by 1.6 times compared with the control. Daily administration of reduced glutathione to animals with nephropathy for 7 days led to a decrease in the level of substances of medium and low molecular weight by 21% and 27% in comparison with the indicators of animals with nephropathy, but still significantly differed from the control indicators. Against the background of an increase in the content of total oligopeptides by 2.2 times in the blood serum of experimental rats, the level of tyrosine-containing peptides increased by 1.8 times in comparison with the control. The introduction of glutathione to rats with nephropathy led to a decrease in these parameters by 40 and 35%, respectively, compared with the experimental control. As a result of the established changes in the level of albumin and average weight molecules in the blood serum of animals, under conditions of nephropathy, an increase in the coefficient of endogenous intoxication was observed by 2.3 times. This imbalance indicates a violation of the processes of detoxification of endogenous metabolites in the liver of animals under conditions of nephropathy. In the groups of animals with nephropathy, which were injected with an antioxidant, the coefficient of endogenous intoxication decreased by 41% compared with animals that did not receive glutathione, but this indicator did not return to the level of control values. Conclusion. Thus, under the conditions of experimental nephropathy in the blood serum of rats, an increase in the content of total and tyrosine-containing peptides, substances of low and medium molecular weight, as well as an increase in the values of the intoxication coefficient was observed, which indirectly indicates a violation of the processes of detoxification of endogenous metabolites in the liver of experimental animals with kidney pathology. In the group of animals with nephropathy that received reduced glutathione for 7 days, only a tendency towards normalization of the studied parameters characterizing the level of endogenous intoxication under conditions of nephropathy was noted

2019 ◽  
Vol 26 (4) ◽  
pp. 56-65
Author(s):  
М. M. Tlish ◽  
Е. К. Popandopulo

Aim. The paper studies the dynamics of the indicators defi ning the antioxidant system (AOS) and endogenous intoxication in patients with microbial eczema (ME) prior to and following treatment.Materials and methods. The experimental group consisted of patients with ME (n=30) and the control group comprising somatically healthy individuals (n=30). In this study, we determined the components of the antioxidant defence system in blood plasma and erythrocyte suspension, as well as assessed endogenous intoxication.Results. The study revealed an imbalance of indicators refl ecting the severity of oxidative stress and endogenous intoxication in patients suffering from ME. Prior to receiving treatment, the experimental group, as compared to the control group, exhibited an increase in catalase activity (CAT) up to 35.93 [32.50; 38.22] mmol / (min • l) (p < 0.001) and glutathione peroxidase (GPx) up to 1194.27 [1069.50; 1375.78] μmol / (min • l) (p < 0.001). In addition, there was a decrease in the activity of superoxide dismutase (SOD) to 13.28 [11.35; 14.10] u/l (p < 0.001), glutathione reductase (GR) to 501.46 [479.77; 542.52] mmol / (min • l) (p < 0.001) and the concentration of reduced glutathione to 1.64 [1.59; 1.78] μmol / ml (p = 0.043). We observed no statistically signifi cant changes in the total antioxidant activity (TAA) of blood plasma (0.59 [0.55;0.62] mg/l; р = 0.375) and the sulphhydryl groups (0.44 [0.41;0.47] ODU; р =0.111). The patients with ME exhibited the syndrome of endogenous intoxication (SEI), accompanied by an increase in the content of medium and low molecular weight molecules in plasma to 12.19 [11.20; 13.37] arb. u. (p < 0.001), with their content in erythrocytes being relatively normal – 15.23 [14.26; 16.44] arb. u. (p = 0.005). Following the treatment, changes in the studied parameters were of a multidirectional character in relation to the control values. An increased level of CAT and GPx (р <0,001), as well as lower values of SOD and GR, continued to be observed (р < 0.001). The TAA in serum (p = 0.308), sulphhydryl groups (p = 0.111) and reduced glutathione (p = 0.107) did not differ signifi cantly from the control values. The treatment did not reverse the SEI: the content of medium and low molecular weight molecules continued to increase in both plasma and erythrocytes, as compared to the control values (p < 0.001 in both cases).Conclusion. The obtained data confi rm the failure of mechanisms underlying antioxidant defence in patients with ME. Despite the attempt of its compensation by increasing the catalase activity, SOD control values were still not reached. An increase in the GPx activity along with a decrease in GR was observed, which could have lead, in turn, to a decrease in the concentration of reduced glutathione. The failure of the antioxidant defence mechanisms is also indicated by an increase in the content of medium and low molecular weight molecules, as well as by the development of the SEI, resulting from the excessive formation of reactive oxygen species and the inability of the antioxidant system to neutralise them.


2018 ◽  
Vol 25 (4) ◽  
pp. 399-407 ◽  
Author(s):  
Іnna Krynytska ◽  
Mariya Marushchak ◽  
Inna Birchenko ◽  
Ivan Klishch

Abstract Background and aims: Diabetes mellitus (DM) is a significant public health issue, being one of the major contributors to morbidity and mortality in the modern societies. Chronic hyperglycemia produces significant physiological, biochemical, and histological changes in the affected organisms. This study aims to evaluate the markers of endogenous intoxication in rats with diabetes mellitus combined with carrageenan-induced enterocolitis. Materials and methods: Diabetes mellitus was induced by a single intraperitoneal administration of streptozotocin (Sigma Aldrich, USA, at a dose of 60 mg/kg body weight). Carrageenan-induced enterocolitis was modeled by giving the animals free access to 1.0 % solution of carrageenan in drinking water for 1 month. The syndrome of endogenous intoxication was assessed by quantification of low and medium molecular weight substances in blood plasma, red blood cell suspension and urine using extraction-spectrophotometric method. Results: The increase in endogenous intoxication in streptozotocin-induced diabetes combined with chronic enterocolitis can mainly be attributed to the catabolic pool of blood plasma substances of low and medium molecular weight. The index of distribution of low- and medium-molecular-weight substances between blood plasma proteins and glycocalyx of erythrocytes in the experimental groups increased simultaneously with the quantities of investigated fractions in the erythrocyte suspension measured at the wavelengths of 242, 254 and 280 nm. Conclusions: We observed upsurge of endogenous intoxication markers in the rats with diabetes mellitus. Endotoxicosis became even more evident in the rats with diabetes mellitus combined with carrageenan-induced enterocolitis.


2021 ◽  
Vol 88 (1-2) ◽  
pp. 39-44
Author(s):  
E. T. Mammadova

Objective. To study the lipid peroxidation processes and endogenous intoxication indicators in patients with widespread peritonitis before surgery and during the treatment. Materials and methods. The study included 97 patients (43 men and 54 women) aged from 17 to 69 years with purulent peritonitis. According to treatment scheme, patients were divided into two groups. Patients in group 1 received standard treatment, and in patients in group 2 standard treatment was supplemented by immunoreactions. The concentration of diene conjugates and malonic dialdehyde, reduced glutathione, catalase activity and the concentration of medium molecular weight peptides were determined in the blood of patients and almost healthy people. Results. The concentration of diene conjugates, malonic dialdehyde and medium molecular weight peptides in the blood of patients with advanced peritonitis increased significantly depending on the clinical stage of the disease, while the activity of the enzyme catalase and the concentration of reduced glutathione were decreased. Conclusions. Immunoreactions in combination with standard treatment leads to normalization of lipid peroxidation and reduction of endogenous intoxication on the 5th and 10th days of treatment.


2017 ◽  
Vol 8 (2) ◽  
pp. 259-264
Author(s):  
P. H. Lyhatskyi ◽  
L. S. Fira ◽  
D. B. Fira ◽  
I. P. Kuzmak

Among pollutants a significant threat is posed by heavy metals, nitrate fertilizers and industrial waste. However, people also contribute to this threat through bad habits such as smoking and alcohol. All these factors affect health and can cause death. The aim of this study was to investigate the content of reactive oxygen species, markers of cytolysis of hepatocytes, cardoza and the degree of endogenous intoxication in the organism of rats affected by nitrite of sodium on the background of tobacco intoxication. The experiments were carried out on white rats, which were divided into three age categories: immature, mature and old, who for 30 days were exposed to tobacco smoke. The research animals were divided into three groups. One of them for 24 hours before the end of the experiment was given sodium nitrite, the second group was given sodium nitrite 72 hours before the end of the experiment. 30 days after poisoning we tested the contents of reactive oxygen species in neutrophils, cytolysis of erythrocyte membrane was investigated by erythrocytic index of intoxication, hepatocytes and cardiocytes – aminotransferase activity. The degree of endogenous intoxication was evaluated by the content of average weight molecules in blood serum. Poisoning of rats with sodium nitrite on the background of the 30 day intoxication by tobacco smoke led to a significant formation of ROS in neutrophils of rats of different age groups. We investigated the activity of aminotransferases in the blood serum and the above organs of rats after exposing them to sodium nitrite and 30 day tobacco smoke. In the blood serum of adult and aged rats, the activity of alanine aminotransferase increased in these conditions by 2.1 and 1.6 times, respectively. Sodium nitrite, which was an additional factor in the intoxication of the rats of all age groups by smoke, caused more pronounced changes in the activity of the studied enzyme in the blood serum. In the liver and myocardium of rats of different ages a reliable decrease of this index was observed in all experimental groups. There was a significant increase in the serum of rats at different ages of aspartate aminotransferase activity. Aspartate aminotransferase activity in the myocardium of all experimental animals showed a reduction by 1.2–1.3 times after smoke inhalation and 1.5–1.6 times with simultaneous intoxication of the rats by sodium nitrite and tobacco smoke. Sodium nitrite, as an additional toxin raised the penetration capacity of erythrocytes among rats poisoned with smoke.By the end of the experiment, the erythrocyte index of intoxication increased in all age groups: immature rats by 31.7%, mature – by 36.0%, in old rats – by 23.6%. The next step of our research was to investigate the markers of endogenous intoxication – average molecular weight. After the simultaneous intoxication of rats by sodium nitrate and tobacco smoke, at the end of the experiment the content of average weight molecules was λ = 254 and of average mass λ=280 inthe blood serum of rats of all age groups increased by 3.1–3.3 times compared with the intact control group. Immature rats proved most sensitive to the action of sodium nitrite and tobacco. 


1973 ◽  
Vol 30 (01) ◽  
pp. 093-105 ◽  
Author(s):  
C.H.J Sear ◽  
L Poller ◽  
F.R.C Path

SummaryThe antiheparin activity of normal serum has been studied by comparing the antiheparin activities of sera obtained from normal whole blood, platelet-rich plasma and platelet-’free’ plasma with a purified platelet extract during differential isoelectric precipitation and by gel filtration chromatography.The mean values for the activity of PRP-serum and PFP-serum were 106% (S.D. 11) and 10% (S.D. 3) of untreated whole blood respectively. The activity of whole blood serum, PRP serum and whole blood serum plus platelet extract precipitated under identical physical conditions, i.e. pH 7.0, I =0.008, indicating that the activities of the three samples are probably associated with PF4. PF4 precipitated from human platelet extract at pH 4.0, but this is probably due to the difference in the two biochemical environments investigated, i.e. serum and platelet extract.The gel filtration experiments revealed striking similarities between the major antiheparin activities of serum and platelet extract. At physiological pH and ionic strength both activities were associated with high molecular weight material, but at physiological pH and elevated ionic strength both activities behaved as much smaller entities of molecular weight between 25,000 and 30,000 daltons and it seems very likely that both activities are associated with the same molecule, i.e. PF4.


Author(s):  
Raghavendra Mitta ◽  
Sushmitha Duddu ◽  
Raghuveer Yadav Pulala ◽  
Pradeepkumar Bhupalam ◽  
Venkatakirankumar Mandlem ◽  
...  

AbstractObjectivesThe main objective of the present study is to evaluate the mitigative effect of hydroalcoholic extract of Momordica cymbalaria fruits against sodium fluoride (NaF) induced hepatotoxicity.MethodsIn this study, Wistar male albino rats were randomly divided into five groups of six rats each. Group I and II served as normal and toxic controls. Group III as plant control received extract at a dose of 400 mg/kg b. wt, p.o and Groups IV and V as treatment groups received extract at a dose 200 and 400 mg/kg b. wt, p.o for 30 days. All groups except Groups I and III received 100 ppm of NaF through drinking water. After completion of the study, blood collected for the estimation of liver blood serum biomarkers such as aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline Phosphatase (ALP), direct and total bilirubin, total protein and albumin. The liver tissue homogenate was for estimation of lipid peroxidation, catalase, and reduced glutathione levels.ResultsThe results showed that NaF intoxication caused elevation of liver blood serum levels and lipid peroxidation; decreased levels of serum total protein, albumin and liver reduced glutathione, and catalase observed. The treatment groups showed decreased elevated serum biomarkers (ALT, AST, and ALP), liver lipid peroxidation and increased serum total protein and albumin, liver reduced glutathione and catalase levels in a dose-dependent manner. Histopathological studies also further strongly supported for mitigative effects of the plant.ConclusionsIn conclusion, our findings of the study indicated that M. cymbalaria fruits were a potential drug candidate in the treatment of NaF induced hepatotoxicity.


Author(s):  
Anna L. Yasenyavskaya ◽  
Alexandra A. Tsibizova ◽  
Lyudmila A. Andreeva ◽  
Nikolay F. Myasoedov ◽  
Olga A. Bashkina ◽  
...  

Objective. To investigate the effect of glyprolines on the levels of initiating and effector caspases in the serum of white rats under "social" stress. Materials and methods. The study was conducted on 90 white male rats of 6 months of age. All manipulations with animals were carried out in accordance with international and domestic requirements for working with laboratory animals. When modeling "social" stress, groups of animals with aggressive and submissive behavior were formed. Laboratory animals, taking into account the types of behavior, were divided into groups (n=10): a group of intact males (control); a group of animals exposed to" social " stress for 20 days (stress); groups of individuals who received intraperitoneal Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), Pro-Gly-Pro, Pro-Gly-Pro-Leu at doses of 100 mcg/kg / day from the 1st day of stress exposure within a 20- day course. The effect of neuropeptides on the activity of apoptosis processes was evaluated by determining the level of initiating and effector caspases (caspase-8 and caspase-3) (ELISA Kit for Caspase-8 and ELISA Kit for Caspase-3; USA) in the blood serum of white rats by enzyme immunoassay. Results. According to the results of the study, it was found that under conditions of "social" stress, an increase in apoptotic processes was observed, accompanied by an increase in the level of caspase-3 and caspase-8 in the blood serum of white rats. The introduction of the studied compounds against the background of stress contributed to a decrease in the level of the studied indicators, which is most likely due to the presence of antiapoptotic action in glyprolins due to inhibition of the caspase-dependent cascade of apoptosis reactions, as a result of which the destruction of cellular structures occurs by hydrolysis of nuclear lamina, cleavage of adhesive proteins, destruction of the cytoskeleton. Conclusion. Thus, the conducted study established the presence of Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank), Pro-Gly-Pro and Pro-Gly-Pro-Leu under conditions of stress-induced antiapoptotic activity due to inhibition of the caspase-dependent cascade of apoptosis reactions.


2015 ◽  
Vol 37 (2) ◽  
pp. 130-134 ◽  
Author(s):  
N I Fedosova ◽  
I M Voeykova ◽  
O M Karaman ◽  
T V Symchych ◽  
G V Didenko ◽  
...  

Aim: To study the effects of xenogeneic cancer vaccine (XCV) developed on the basis of nervous tissue antigen from rat embryo of late gestation period and protein-containing metabolite of Bacillus subtilis with molecular weight of 70 kDa, on specific and unspecific antitumor reactions of cellular and humoral chains of immune system, and to analyze possible mechanisms of its antimetastatic action. Materials and Methods: XCV was administered triply with 3-day intervals after surgical removal of experimental melanoma В-16 in C57Bl/6 mice. Cytotoxic activity (CTA) of splenocytes against target cells К-562 as well as CTA of splenocytes, peritoneal macrophages (PM) and blood serum against melanoma В-16 target cells were determined using МТТ test. The content of circulating immune complexes (CIC) in blood serum was evaluated by precipitation reaction. Results: Immunologic effects of XCV vaccination in experimental animals with surgically removed melanoma B-16 in comparison with similarly treated unvaccinated mice were as follows: prevention of medium molecular weight CIC accumulation in blood serum during all observation period, significant increase (р < 0.05) of CTA of effectors of unspecific antitumor immunity (natural killer cells — NK — by 25.5 ± 1.7 vs 12.5 ± 5.4%, and PM — by 37.3 ± 0.6 vs 32.0 ± 0.9%, respectively) at 37th day after the surgery, and also preservation of functional activity of specific cytotoxic lymphocytes at the level of intact control. Conclusion: The results of the study allow propose that antimetastatic effect of XCV vaccination could be based on increased CTA of NK and PM, and preservation of CTL functional activity at late terms after surgical removal of B-16 primary tumors.


2016 ◽  
Vol 8 (24) ◽  
pp. 4835-4843 ◽  
Author(s):  
Jeanne V. Samsonova ◽  
Anastasia D. Chadina ◽  
Alexander P. Osipov ◽  
Sergey E. Kondakov

Applicability of a new and simple membrane-strip microsampling format for the analysis of human blood serum in a strip-dried form for the presence of a range of model low and high molecular weight analytes by ELISA was demonstrated.


Blood ◽  
1949 ◽  
Vol 4 (10) ◽  
pp. 1142-1155 ◽  
Author(s):  
GEORGE M. HIGGINS ◽  
MURIEL STEMBER ◽  
HARRY MONSEN

Abstract A study of some of the toxic reactions of 4-aminofolic acid together with the modifications of these reactions induced by giving varying amounts of folic acid daily to white rats is reported. Seven groups of young male rats ranging in weight from 110 to 130 Gm. were arranged. Aminopterin (4-aminofolic acid) was given intraperitoneally, in amounts equivalent to 50 micrograms daily, to all rats of six of these seven groups. Folic acid was given by mouth to these animals in such amounts as to provide 5, 10, 20, 30 or 50 mg. daily to each animal respectively of five of the six groups receiving aminopterin. One group received the analogue without the vitamin. One group of 8 animals received neither the vitamin nor its analogue. Observations continued for six days, when all surviving animals were killed and necropsy was performed. Data were assembled on the appetite, body weights, the weights of adrenals, thymus and spleen, the distribution of leukocytes in the peripheral blood and the changes in the bone marrow. The following conclusions seem warranted: 1. Aminopterin is extremely toxic and incites within six days anorexia, extreme diarrhea with atony of the entire gastro-intestinal tract, adrenal hyperplasia, atrophy of the thymus and spleen, and an inhibition to development of myeloid cells in the bone marrow. 2. Small amounts of folic acid are essentially without effect on the toxicity of that amount of the analogue we chose to administer. 3. Larger amounts of folic acid daily (30 mg.) proved effective in essentially inhibiting the development of the severe toxic reactions for the six-day period. 4. The severe toxicity of aminopterin does not manifest itself until the third or or fourth day of its daily administration. The onset of these symptoms is thereafter extremely rapid. 5. Thirty milligrams of folic acid daily will not indefinitely counteract the toxic symptoms induced by 50 micrograms of aminopterin. In our experience, within twelve to fourteen days, the characteristic syndrome will appear in spite of the continuous administration of the vitamin.


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